Effects of Severe Hypoglycemia on Cardiovascular Outcomes and Death in the Veterans Affairs Diabetes Trial.

OBJECTIVE: To determine the risk factors for severe hypoglycemia and the association between severe hypoglycemia and serious cardiovascular adverse events and cardiovascular and all-cause mortality in the Veterans Affairs Diabetes Trial (VADT). RESEARCH DESIGN AND METHODS: This post hoc analysis of data from the VADT included 1,791 military veterans (age 60.5 ± 9.0 years) with suboptimally controlled type 2 diabetes (HbA1c 9.4 ± 2.0%) of 11.5 ± 7.5 years disease duration with or without known cardiovascular disease and additional cardiovascular risk factors. Participants were randomized to intensive (HbA1c <7.0%) versus standard (HbA1c <8.5%) glucose control. RESULTS: The rate of severe hypoglycemia in the intensive treatment group was 10.3 per 100 patient-years compared with 3.7 per 100 patient-years in the standard treatment group (P < 0.001). In multivariable analysis, insulin use at baseline (P = 0.02), proteinuria (P = 0.009), and autonomic neuropathy (P = 0.01) were independent risk factors for severe hypoglycemia, and higher BMI was protective (P = 0.017). Severe hypoglycemia within the past 3 months was associated with an increased risk of serious cardiovascular events (P = 0.032), cardiovascular mortality (P = 0.012), and total mortality (P = 0.024). However, there was a relatively greater increased risk for total mortality in the standard group compared with the intensive group (P = 0.019). The association between severe hypoglycemia and cardiovascular events increased significantly as overall cardiovascular risk increased (P = 0.012). CONCLUSIONS: Severe hypoglycemic episodes within the previous 3 months were associated with increased risk for major cardiovascular events and cardiovascular and all-cause mortality regardless of glycemic treatment group assignment. Standard therapy further increased the risk for all-cause mortality after severe hypoglycemia.

Cost and Utility Analysis of a Store-and-Forward Teledermatology Referral System: A Randomized Clinical Trial.

IMPORTANCE: The costs and utility of teledermatology are important features of implementation. Such an analysis requires a description of the perspective of the entity that will bear the cost. OBJECTIVE: To assess the costs and utility of a store-and-forward teledermatology referral process compared with a conventional referral process from the perspectives of the Department of Veterans Affairs (VA) and society. DESIGN, SETTING, AND PARTICIPANTS: Three hundred ninety-one randomized participants were referred from remote sites of primary care to the dermatology services of 2 VA medical facilities for ambulatory skin conditions from December 2008 through June 2010, and follow-up was completed in March 2011. The time trade-off utility measures and costs were collected during a 9-month period among participants in a 2-site parallel group randomized clinical trial. The perspectives of the VA and society were evaluated. The multiple imputation procedure or weighted means were used for missing data elements. Data were analyzed from January to July 2014. INTERVENTIONS: Referrals were managed using store-and-forward teledermatology or a conventional text-based referral process. MAIN OUTCOMES AND MEASURES: Total costs from the perspectives of the VA and society incurred during the 9-month follow-up were used to derive per-participant costs. Utility, using the time trade-off method, was the measure of effectiveness. RESULTS: From the VA perspective, the total cost for conventional referrals was $66 145 (minimum, $58 697; maximum, $71 635), or $338 (SD, $291) per participant (196 participants); the total cost for teledermatology referrals was $59 917 (mimimum, $51 794; maximum, $70 398), or $308 (SD, $298) per participant (195 participants). The $30 difference in per-participant cost was not statistically significant (95% CI, -$79 to $20). From the societal perspective, the total cost for conventional referrals was $106 194 (minimum, $98 746; maximum, $111 684), or $542 (SD, $403) per participant (196 participants); the total cost for teledermatology referrals was $89 523 (minimum, $81 400; maximum, $100 400) or $460 (SD, $428) per participant. This $82 difference in per-participant cost was statistically significant (95% CI, -$12 to -$152). From baseline to the 9-month follow-up, the time trade-off utility value improved by 0.02 in the conventional referral group and 0.03 in the teledermatology group. This difference was not statistically significant (P = .50). CONCLUSIONS AND RELEVANCE: Compared with conventional referrals, store-and-forward teledermatology referrals were performed at a comparable cost (VA perspective) or at a lower cost (societal perspective) with no evidence of a difference in utility as measured by the time trade-off method. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00488293.

Clinical course outcomes for store and forward teledermatology versus conventional consultation: a randomized trial.

We assessed the clinical course of patients after store and forward teledermatology in comparison with conventional consultations. Patients being referred from primary care to dermatology clinics were randomly assigned to teledermatology or a conventional consultation. A total of 392 patients were randomized; 261 patients completed the study and were included in the analysis. Their clinical course was rated on a five-point scale by a panel of three dermatologists, blinded to study assignment, who reviewed serial digital image sets. The clinical course was assessed by comparing images sets between baseline and first clinic visit (if one occurred) and between baseline and nine months. There was no evidence to suggest a difference between the two groups in either clinical course between baseline and nine months post-referral (P = 0.88) or between baseline and the first dermatology clinic visit (P = 0.65). Among teledermatology referrals, subsequent presentation for an in-person dermatology clinic visit was significantly correlated with clinical course (P = 0.023). Store and forward teledermatology did not result in a significant difference in clinical course at either of two post-referral time periods.

Effect of store and forward teledermatology on quality of life: a randomized controlled trial.

IMPORTANCE: Although research on quality of life and dermatologic conditions is well represented in the literature, information on teledermatology's effect on quality of life is virtually absent. OBJECTIVE: To determine the effect of store and forward teledermatology on quality of life. DESIGN: Two-site, parallel-group, superiority randomized controlled trial. SETTING: Dermatology clinics and affiliated sites of primary care at 2 US Department of Veterans Affairs medical facilities. PARTICIPANTS: Patients being referred to a dermatology clinic were randomly assigned, stratified by site, to teledermatology or the conventional consultation process. Among the 392 patients who met the inclusion criteria and were randomized, 326 completed the allocated intervention and were included in the analysis. INTERVENTIONS: Store and forward teledermatology (digital images and a standardized history) or conventional text-based consultation processes were used to manage the dermatology consultations. Patients were followed up for 9 months. MAIN OUTCOME MEASURES: The primary end point was change in Skindex-16 scores, a skin-specific quality-of-life instrument, between baseline and 9 months. A secondary end point was change in Skindex-16 scores between baseline and 3 months. RESULTS: Patients in both randomization groups demonstrated a clinically significant improvement in Skindex-16 scores between baseline and 9 months with no significant difference by randomization group (P = .66, composite score). No significant difference in Skindex-16 scores by randomization group between baseline and 3 months was found (P = .39, composite score). CONCLUSIONS: Compared with the conventional consultation process, store and forward teledermatology did not result in a statistically significant difference in skin-related quality of life at 3 or 9 months after referral. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00488293.

The use of zoledronic acid in men receiving androgen deprivation therapy for prostate cancer with severe osteopenia or osteoporosis.

OBJECTIVES: To study the effect of zoledronic acid on patients with pre-existing osteoporosis on androgen deprivation therapy (ADT), who are at highest risk for fracture. Zoledronic acid is a potent bisphosphonate that can prevent osteoporosis in patients with nonmetastatic (M0), prostate cancer (CaP) who are initiating ADT. The effect of zoledronic acid on patients with pre-existing osteoporosis on ADT, who are highest risk for fracture, has not been adequately studied. METHODS: We enrolled 28 patients with M0 CaP on ADT with severe osteopenia or osteoporosis (baseline bone-mineral density (BMD) T score < -2.0) in this open-label, single-arm trial to assess the effect of zoledronic acid on BMD. All patients also received supplemental calcium and vitamin D, and were counseled about lifestyle modifications. Patients received zoledronic acid (4 mg) intravenously every 3 months for 4 treatments. BMD was measured by dual energy X-ray absorptiometry scan at enrollment, 6 and 12 months. Primary endpoint was percent change in lumbar spine BMD. RESULTS: This was a high-risk patient population-primarily older Caucasians (mean age, 73 years), former smokers, and moderate users of alcohol. Mean duration of ADT was 2.4 years. Pre-existing osteopenia or osteoporosis was observed in a single site in 9 patients and multiple sites in 19 (68%). After 12 months of zoledronic acid, lumbar spine BMD increased 4.17% (P < .0001), and BMD increased significantly (P < .05) in both hips and the right femoral neck. Seven patients (25%) experienced improved BMD into the nonosteoporotic range (T score > -2.0). Zoledronic acid infusion was well tolerated and without substantial renal toxicity. CONCLUSIONS: Zoledronic acid improves BMD in men with M0 CaP on ADT with severe osteopenia or osteoporosis (T scores < 2.0). This novel finding identifies a high-risk patient population that can potentially benefit from bisphosphonate therapy.

Ethnicity, race, and clinically significant macular edema in the Veterans Affairs Diabetes Trial (VADT).

OBJECTIVE: To determine risk factors in clinically significant macular edema (CSME) and if increased CSME in minorities is due to ethnicity or other factors in the Veterans Affairs Diabetes Trial (VADT). METHODS: CSME prevalence based on 7-field stereo fundus photographs in 1268 patients with type 2 diabetes was related to ethnicity, demographics and biochemistries by univariate and multivariate analyses. RESULTS: Hispanics (H) made up 17.5% and African Americans (AA) 17.7% of the cohort. CSME prevalence was 10%. In univariate analysis, CSME was more prevalent in H, 18%, and AA, 15.6% than in non-Hispanic Whites (NHW), 6.3%, p<0.01. Univariate regression of CSME associated with younger age, younger onset of diabetes; longer duration; retinopathy severity; and high HbA1c, BP, urine albumin/creatinine, and amputation, all p<0.01. In multivariate regression, CSME was associated with ethnicity/race (Hispanic White vs. non-Hispanic White, OR, (95% CI), 2.30, (1.35-3.92), p<0.01; African American vs. non-Hispanic White, 2.30, (1.33-4.00), p<0.01), diastolic BP (1.13 per 5 mm Hg, (1.02-1.23), p=0.03), amputation (3.0, (1.11-8.13), p=0.04), and retinopathy severity ( approximately 30, ( approximately 17 to approximately 59), p<0.01). CONCLUSION: The prevalence of CSME in the VADT is associated with ethnicity as well as diastolic BP, amputation, and retinopathy severity.

Usefulness of revascularization of patients with multivessel coronary artery disease before elective vascular surgery for abdominal aortic and peripheral occlusive disease.

The Coronary Artery Revascularization Prophylaxis (CARP) study showed no survival benefit with preoperative coronary artery revascularization before elective vascular surgery. The generalizability of the trial results to all patients with multivessel coronary artery disease (CAD) has been questioned. The objective of this study was to determine the impact of prophylactic coronary revascularization on long-term survival in patients with multivessel CAD. Over a 4-year period, 1,048 patients underwent coronary angiography before vascular surgery during screening into the CARP trial. The cohort was composed of registry (n = 586) and randomized (n = 462) patients, and their survival was determined at 2.5 years after vascular surgery. High-risk coronary anatomy without previous bypass surgery included 2-vessel disease (n = 204 [19.5%]), 3-vessel disease (n = 130 [12.4%]), and left main coronary artery stenosis > or = 50% (n = 48 [4.6%]). By log-rank test, preoperative revascularization was associated with improved survival in patients with a left main coronary artery stenoses (0.84 vs 0.52, p <0.01) but not those with either 2-vessel (0.80 vs 0.79, p = 0.83) or 3-vessel (0.79 vs 0.71, p = 0.15) disease. In conclusion, unprotected left main coronary artery disease was present in 4.6% of patients who underwent coronary angiography before vascular surgery, and this was the only subset of patients showing a benefit with preoperative coronary artery revascularization.

Predictors and outcomes of a perioperative myocardial infarction following elective vascular surgery in patients with documented coronary artery disease: results of the CARP trial.

AIMS: The predictors and outcomes of patients with a peri-operative elevation in cardiac troponin I above the 99th percentile of normal following an elective vascular operation have not been studied in a homogeneous cohort with documented coronary artery disease. METHODS AND RESULTS: The Coronary Artery Revascularization Prophylaxis (CARP) trial was a randomized trial that tested the benefit of coronary artery revascularization prior to vascular surgery. Among 377 randomized patients, core lab samples for peak cardiac troponin I concentrations were monitored following the vascular operation and the blinded results were correlated with outcomes. A peri-operative myocardial infarction (MI), defined by an increase in cardiac troponin I greater than the 99th percentile reference (> or =0.1 microg/L), occurred in 100 patients (26.5%) and the incidence was not dissimilar in patients with and without pre-operative coronary revascularization (24.2 vs. 28.6%; P = 0.32). By logistic regression analysis, predictors of MI (odds risk; 95%CI; P-value) were age >70 (1.84; 1.14-2.98; P = 0.01), abdominal aortic surgery (1.82; 1.09-3.03; P = 0.02), diabetes (1.86; 1.11-3.11; P = 0.02), angina (1.67; 1.03-2.64; P = 0.04), and baseline STT abnormalities (1.62; 1.00-2.6; P = 0.05). At 2.5 years post-surgery, the probability of survival in patients with and without the MI was 0.73 and 0.84, respectively (P = 0.03, log-rank test). Using a Cox proportional hazards regression analysis, a peri-operative MI in diabetic patients was a strong predictor of long-term mortality (hazards ratio: 2.43; 95% CI: 1.31-4.48; P < 0.01). CONCLUSION: Among patients with coronary artery disease who undergo vascular surgery, a peri-operative elevation in cardiac troponin levels is common and in combination with diabetes, is a strong predictor of long-term mortality. These data support the utility of cardiac troponins as a means of stratifying high-risk patients following vascular operations.

Coronary artery bypass grafting is superior to percutaneous coronary intervention in prevention of perioperative myocardial infarctions during subsequent vascular surgery.

BACKGROUND: Among patients in need of coronary revascularization before an elective vascular operation, the value of coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in preventing perioperative myocardial infarctions is uncertain. We hypothesized that more complete revascularization would improve outcomes after vascular surgery. METHODS: In this Veterans Affairs Cooperative trial involving 18 medical centers, 222 patients underwent elective vascular surgery after coronary revascularization. The mode of coronary revascularization was selected at each site by the local investigators (CABG in 91 patients and PCI in 131 patients). The vascular surgical indications were similar in both groups. RESULTS: There were 2 deaths in the CABG group (2.2%) and 5 deaths in the PCI group (3.8%; p = 0.497) after the vascular procedure. There were fewer perioperative myocardial infarctions after the vascular operation in CABG patients (6.6%) than in PCI patients (16.8%; p = 0.024), despite more diseased vessels in the CABG group (3.0 +/- 1.3 versus 2.2 +/- 1.4, respectively; p < 0.001). The completeness of revascularization (defined as the number of coronary artery vessels revascularized relative to the total number of vessels with a stenosis > or = 70%) in patients in the CABG and PCI groups was 117% +/- 63% and 81% +/- 57%, respectively (p < 0.001). Hospital length of stay in CABG versus PCI patients was 6 (4, 8) and 7 (4, 10) days, respectively (p = 0.078). CONCLUSIONS: Among patients receiving multivessel coronary artery revascularization as prophylaxis for elective vascular surgery, patients having a CABG had fewer myocardial infarctions and tended to spend less time in the hospital after the vascular operation than patients having a PCI. More complete revascularization accounted for the intergroup differences.

Postoperative outcomes for patients undergoing elective revascularization for critical limb ischemia and intermittent claudication: a subanalysis of the Coronary Artery Revascularization Prophylaxis (CARP) trial.

OBJECTIVE: To determine the perioperative mortality, myocardial infarction rate, and long-term survival of patients with critical limb ischemia (CLI) compared with those with intermittent claudication (IC) within a cohort selected for significant coronary artery disease, a secondary analysis was conducted of a prospective, randomized, multicenter trial of Coronary Artery Revascularization Prophylaxis (CARP) before peripheral vascular surgery. This multicenter trial was sponsored by the Cooperative Studies Program of the Department of Veterans Affairs. METHODS: Of the 510 patients enrolled in the CARP trial and randomized to coronary revascularization or no revascularization before elective vascular surgery, 143 had CLI and 164 had IC as an indication for lower limb revascularization; >95% of each group were men. The presence of coronary artery disease was determined by cardiac catheterization. Eligible patients had at least one treatable coronary lesion of > or =70%. Those with significant left main disease, ejection fraction of <20%, and aortic stenosis were excluded. Patients were randomized to coronary artery disease revascularization or no revascularization before vascular surgery and followed for mortality and morbidity perioperatively and for a median of 2.7 years postoperatively. Medical treatment of coronary artery disease was pursued aggressively. RESULTS: Patients with IC had a longer time from randomization to vascular surgery (p = .001) and more abdominal operations (p < .001). Patients with CLI had more urgent operations (p = .006), reoperations (p < .001), and limb loss (p = .008) as well as longer hospital stays (p < .001). The IC group had more perioperative myocardial infarctions (CLI, 8.4%; IC, 17.1%; p = .024), although perioperative mortality was similar (CLI, 3.5%; IC, 1.8%; p = .360). In follow-up, the IC group also had numerically more myocardial infarctions (CLI, 16.8%; IC, 25%; p = .079), but mortality was not different (CLI, 21%; IC, 22%; p = .825). Coronary artery revascularization did not lower perioperative or long-term mortality in either group. CONCLUSIONS: Our data indicate that patients with significant coronary artery disease and either CLI or IC can undergo vascular surgery with low mortality and morbidity, and these results are not improved by coronary artery revascularization before vascular surgery. Furthermore, when selected for the presence of symptomatically stable, severe coronary artery disease, there is no difference in long-term survival between patients with CLI and IC. Finally, the better-than-predicted outcomes for these patients with advanced systemic atherosclerosis may be due to aggressive medical management with beta-blockers, statins, and acetylsalicylic acid.

Long-term patency of saphenous vein and left internal mammary artery grafts after coronary artery bypass surgery: results from a Department of Veterans Affairs Cooperative Study.

OBJECTIVES: This study defined long-term patency of saphenous vein grafts (SVG) and internal mammary artery (IMA) grafts. BACKGROUND: This VA Cooperative Studies Trial defined 10-year SVG patency in 1,074 patients and left IMA patency in 457 patients undergoing coronary artery bypass grafting (CABG). METHODS: Patients underwent cardiac catheterizations at 1 week and 1, 3, 6, and 10 years after CABG. RESULTS: Patency at 10 years was 61% for SVGs compared with 85% for IMA grafts (p < 0.001). If a SVG or IMA graft was patent at 1 week, that graft had a 68% and 88% chance, respectively, of being patent at 10 years. The SVG patency to the left anterior descending artery (LAD) (69%) was better (p < 0.001) than to the right coronary artery (56%), or circumflex (58%). Recipient vessel size was a significant predictor of graft patency, in vessels >2.0 mm in diameter SVG patency was 88% versus 55% in vessels 2.0 mm in diameter.

Coronary-artery revascularization before elective major vascular surgery.

BACKGROUND: The benefit of coronary-artery revascularization before elective major vascular surgery is unclear. METHODS: We randomly assigned patients at increased risk for perioperative cardiac complications and clinically significant coronary artery disease to undergo either revascularization or no revascularization before elective major vascular surgery. The primary end point was long-term mortality. RESULTS: Of 5859 patients scheduled for vascular operations at 18 Veterans Affairs medical centers, 510 (9 percent) were eligible for the study and were randomly assigned to either coronary-artery revascularization before surgery or no revascularization before surgery. The indications for a vascular operation were an expanding abdominal aortic aneurysm (33 percent) or arterial occlusive disease of the legs (67 percent). Among the patients assigned to preoperative coronary-artery revascularization, percutaneous coronary intervention was performed in 59 percent, and bypass surgery was performed in 41 percent. The median time from randomization to vascular surgery was 54 days in the revascularization group and 18 days in the group not undergoing revascularization (P<0.001). At 2.7 years after randomization, mortality in the revascularization group was 22 percent and in the no-revascularization group 23 percent (relative risk, 0.98; 95 percent confidence interval, 0.70 to 1.37; P=0.92). Within 30 days after the vascular operation, a postoperative myocardial infarction, defined by elevated troponin levels, occurred in 12 percent of the revascularization group and 14 percent of the no-revascularization group (P=0.37). CONCLUSIONS: Coronary-artery revascularization before elective vascular surgery does not significantly alter the long-term outcome. On the basis of these data, a strategy of coronary-artery revascularization before elective vascular surgery among patients with stable cardiac symptoms cannot be recommended.

Risk factors and mortality associated with Clostridium difficile-associated diarrhoea at a VA hospital.

The objective of this study was to evaluate the risk of certain patient co-morbidities and antibiotics in the development of Clostridium difficile-associated diarrhoea (CDAD). Hospitalized patients developing CDAD during a specified period were compared with a cohort of patients, matched by age, without a diagnosis of CDAD, who were hospitalized during the same time period. Data collection included demographics, hospital ward, co-morbid conditions, antibiotics received, and mortality. Gender and age were similar in both groups. Co-morbid conditions significantly associated with the case group included cancer and COPD. The most commonly prescribed antibiotics in the case versus control group included levofloxacin, intravenous vancomycin, clindamycin, and piperacillin/tazobactam. The case group was associated with a higher mortality rate.

Relationship between processes of care and coronary bypass operative mortality and morbidity.

BACKGROUND: Information is limited regarding the effects of processes of care on cardiac surgical outcomes. Correspondingly, many recommended cardiac surgical processes of care are derived from animal experiments or clinical judgment. This report from the VA Cooperative Study in Health Services, "Processes, Structures, and Outcomes of Cardiac Surgery," focuses on the relationships between 3 process groups (preoperative evaluation, intraoperative care, and supervision by senior physicians) and a composite outcome, perioperative mortality and morbidity. METHODS: Data on 734 risk, process, and structure variables were collected prospectively on 3,988 patients who underwent coronary artery bypass grafting at 14 VA medical centers between 1992 and 1996. Data reduction was accomplished by examining data completeness and variation across sites and surgeon, using previously published data and clinical judgment. We then applied multivariable logistic regression to the 39 remaining processes of care to determine which were related to the composite outcome after adjusting for 17 patient-related risk factors and controlling for intraoperative complications. RESULTS: Our first analysis showed several measures of operative duration, the use of inotropic agents, transesophageal echo, lowest systemic temperature, and hemoconcentration/ultrafiltration, to be powerful predictors of the composite outcome. Because the use of inotropic agents and operative duration may be related to an intermediate outcome (eg, intraoperative complications), we performed a second analysis omitting these processes. The use of intraoperative transesophageal echo and hemoconcentration/ultrafiltration remained significantly associated with an increased risk of an event (odds ratios 1.60 and 1.36, respectively). CONCLUSIONS: Our results viewed in the context of past studies suggest the possibility that inotropic use, TEE, and hemoconcentration/ultrafiltration may have adverse effects on operative outcome. Further evaluation of these processes of care using observational data, as well as randomized trials when feasible, would be of interest.